Establishment of a specimen panel for the decentralised technical evaluation of the sensitivity of 31 rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021

Abstract

Introduction The detection of SARS-CoV-2 with rapid diagnostic tests (RDT) has become an important tool to identify infected people and break infection chains. These RDT are usually based on antigen detection in a lateral flow approach. Aim We aimed to establish a comprehensive specimen panel for the decentralised technical evaluation of SARS-CoV-2 antigen rapid diagnostic tests. Methods While for PCR diagnostics the validation of a PCR assay is well established, there is no common validation strategy for antigen tests, including RDT. In this proof-of-principle study we present the establishment of a panel of 50 pooled clinical specimens that cover a SARS-CoV-2 concentration range from 1.1 × 109 to 420 genome copies per mL of specimen. The panel was used to evaluate 31 RDT in up to six laboratories. Results Our results show that there is considerable variation in the detection limits and the clinical sensitivity of different RDT. We show that the best RDT can be applied to reliably identify infectious individuals who present with SARS-CoV-2 loads down to 106 genome copies per mL of specimen. For the identification of infected individuals with SARS-CoV-2 loads corresponding to less than 106 genome copies per mL, only three RDT showed a clinical sensitivity of more than 60%. Conclusions Sensitive RDT can be applied to identify infectious individuals with high viral loads but not to identify all infected individuals.

Impaired detection of omicron by SARS-CoV-2 rapid antigen tests

“…Interestingly, there was a trend for a slightly better detection of cell-culture expanded omicron compared to delta, in particular for tests 2, 4, 6 and 7. In summary, this analysis confirms first studies by other laboratories [14,35] [21,36]. This allowed us to plot and compare the percentages of test samples that scored positive in one of the three categories of Ct/Cp values, i.e.…”

“…and Scheiblauer et al . [ 21 , 36 ]. This allowed us to plot and compare the percentages of test samples that scored positive in one of the three categories of Ct/Cp values, i.e.…”

“… * Data published by Puyskens et al . (collected between March and September 2020 (Panel 1V1; [ 36 ]) and Scheiblauer et al . (additionally collected between October 2020 and January 2021 (Panel 1V2); [ 21 ]) and “SARS-CoV-2 antigen rapid diagnostic tests passing the sensitivity criteria” of the Paul-Ehrlich-Institute (date of access: 31.1.22) 1 The Ct values of test specimens in the study performed by the Paul-Ehrlich-Institute and our study were harmonized to allow a direct comparison of data sets.…”

“…Limitations of the current study include the lack of information on the vaccination status, previous infections, symptoms or stage of COVID-19 of individuals from whom the respiratory swabs were taken. We focused on the analytical sensitivity in relation to the viral loads in respiratory swabs to allow a direct comparison of specimens containing omicron and delta (the current study) and “non-omicron/non-delta” SARS-CoV-2 (studies by the Paul-Ehrlich-Institute [ 21 , 36 ]) in the assessment of RAT performance.…”

Measuring diagnostic performance of COVID-19 tests: lessons for the next pandemic

“…Three notable papers published over the last 2 weeks in Eurosurveillance address the performance of COVID-19 diagnostics. Puysknes et al report the setup of a decentralised evaluation approach and on the technical evaluation of 31 RDT for SARS-CoV-2 antigen detection based on lateral flow [ 2 ]. Using a panel of 50 pooled clinical specimens, representing a wide range of virus concentrations, the 31 evaluated assays demonstrated considerable variation in analytical and clinical sensitivity.…”